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Antidepressant Use and Risk of Incident Cardiovascular Morbidity and Mortality Among Postmenopausal Women in the Women's Health Initiative Study
Jordan W. Smoller, MD, ScD;
Matthew Allison, MD, MPH;
Barbara B. Cochrane, PhD, RN;
J. David Curb, MD, MPH;
Roy H. Perlis, MD, MSc;
Jennifer G. Robinson, MD, MPH;
Milagros C. Rosal, PhD;
Nanette K. Wenger, MD;
Sylvia Wassertheil-Smoller, PhD
Arch Intern Med. 2009;169(22):2128-2139.
Background Antidepressants are commonly prescribed medications, but their effect on cardiovascular morbidity and mortality remains unclear.
Methods Prospective cohort study of 136 293 community-dwelling postmenopausal women in the Women's Health Initiative (WHI). Women taking no antidepressants at study entry and who had at least 1 follow-up visit were included. Cardiovascular morbidity and all-cause mortality for women with new antidepressant use at follow-up (n = 5496) were compared with those characteristics for women taking no antidepressants at follow-up (mean follow-up, 5.9 years).
Results Antidepressant use was not associated with coronary heart disease (CHD). Selective serotonin reuptake inhibitor (SSRI) use was associated with increased stroke risk (hazard ratio [HR],1.45, [95% CI, 1.08-1.97]) and all-cause mortality (HR,1.32 [95% CI, 1.10-1.59]). Annualized rates per 1000 person-years of stroke with no antidepressant use and SSRI use were 2.99 and 4.16, respectively, and death rates were 7.79 and 12.77. Tricyclic antidepressant (TCA) use was associated with increased risk of all-cause mortality (HR,1.67 [95% CI, 1.33-2.09]; annualized rate, 14.14 deaths per 1000 person-years). There were no significant differences between SSRI and TCA use in risk of any outcomes. In analyses by stroke type, SSRI use was associated with incident hemorrhagic stroke (HR, 2.12 [95% CI, 1.10-4.07]) and fatal stroke (HR, 2.10 [95% CI, 1.15-3.81]).
Conclusions In postmenopausal women, there were no significant differences between SSRI and TCA use in risk of CHD, stroke, or mortality. Antidepressants were not associated with risk of CHD. Tricyclic antidepressants and SSRIs may be associated with increased risk of mortality, and SSRIs with increased risk of hemorrhagic and fatal stroke, although absolute event risks are low. These findings must be weighed against quality of life and established risks of cardiovascular disease and mortality associated with untreated depression.
Author Affiliations: Department of Psychiatry, Massachusetts General Hospital, Boston (Drs Smoller and Perlis); Department of Family and Preventive Medicine, School of Medicine, University of California San Diego, La Jolla (Dr Allison); Department of Family & Child Nursing, University of Washington, Seattle (Dr Cochrane); Department of Geriatric Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu (Dr Curb); Departments of Epidemiology & Medicine, University of Iowa, Iowa City (Dr Robinson); Division of Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester (Dr Rosal); Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia (Dr Wenger); and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Wassertheil-Smoller).
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